In Vivo Enrichment of Diabetogenic T Cells.

Abstract:

:Dysfunctional T cells can mediate autoimmunity, but the inaccessibility of autoimmune tissues and the rarity of autoimmune T cells in the blood hinder their study. We describe a method to enrich and harvest autoimmune T cells in vivo by using a biomaterial scaffold loaded with protein antigens. In model antigen systems, we found that antigen-specific T cells become enriched within scaffolds containing their cognate antigens. When scaffolds containing lysates from an insulin-producing β-cell line were implanted subcutaneously in autoimmune diabetes-prone NOD mice, β-cell-reactive T cells homed to these scaffolds and became enriched. These T cells induced diabetes after adoptive transfer, indicating their pathogenicity. Furthermore, T-cell receptor (TCR) sequencing identified many expanded TCRs within the β-cell scaffolds that were also expanded within the pancreata of NOD mice. These data demonstrate the utility of biomaterial scaffolds loaded with disease-specific antigens to identify and study rare, therapeutically important T cells.

journal_name

Diabetes

journal_title

Diabetes

authors

Thelin MA,Kissler S,Vigneault F,Watters AL,White D,Koshy ST,Vermillion SA,Mooney DJ,Serwold T,Ali OA

doi

10.2337/db16-0946

subject

Has Abstract

pub_date

2017-08-01 00:00:00

pages

2220-2229

issue

8

eissn

0012-1797

issn

1939-327X

pii

db16-0946

journal_volume

66

pub_type

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